20 research outputs found
Impact du ciblage du domaine de liaison de HIF-1α avec HIF-1β sur le paysage immunitaire du mélanome
No full textHypoxia is a major feature of solid tumors and is able to induce a tumor immunosuppressive microenvironment. Here, we investigated the impact of inhibiting of the binding domain of HIF-1α to HIF-1β on the immune landscape of B16-F10 melanoma. Targeting this binding domain inhibits the transcriptional activity of HIF-1α in B16-F10 cells in vitro. In vivo, inhibiting the transcriptional activity of HIF-1α in B16-F10 melanoma shows a significant decrease in tumor growth and a consistent improvement in mice survival. Tumor growth is restored in immunodeficient mice, highlighting the critical role of the immune system in controlling melanoma growth. The phenotyping of intra-melanoma immune cells reveals an increase in Natural Killer (NK), CD4+ T cells, regulatory T cells, M1 and M2 macrophages and dendritic cells. NK depletion restores tumor growth in our experimental model, highlighting the role of NK cells in melanoma surveillance. The alteration of the immune landscape that we observed also correlates with a clear increase of secreted CCL5 and CCL2. In conclusion, this study highlights the role of HIF-1α in controlling the growth and the immune landscape of B16-F10 melanoma. It indicates the opportunity of combining HIF-1α inhibitors with immune checkpoint blockade to extend immune checkpoint blockade efficiency and therapeutic benefit to a larger number of cancer patients.L’hypoxie est une caractéristique majeure des tumeurs solides et elle est capable d’induire un microenvironnement tumoral immunosuppressif. Nous avons étudié l’impact de l’inhibition du domaine de liaison de HIF-1α avec HIF-1β sur le paysage immunitaire du mélanome murin B16-F10. Le ciblage de ce domaine de liaison inhibe l’activité transcriptionnelle de HIF-1α dans les cellules B16-F10 in vitro. In vivo, l’inhibition de l’activité transcriptionnelle de HIF-1α dans le mélanome B16-F10 montre une diminution significative de la croissance tumorale et une amélioration consistante de la survie des souris. La croissance tumorale est restaurée dans les souris immunodéficientes, soulignant l’importance du système immunitaire dans le contrôle de la croissance du mélanome. L’étude du phénotype des cellules immunitaires intra-tumorales révèle une augmentation de l’infiltration des cellules Natural Killer (NK), des lymphocytes T CD4+, des T régulateurs, des macrophages de type M1 et M2 et des cellules dendritiques lorsque l’activité transcriptionnelle de HIF-1α est inhibée. La déplétion de cellules NK dans notre modèle expérimental restaure la croissance tumorale, soulignant le rôle des NK dans la surveillance du mélanome B16-F10. Le changement du paysage immunitaire observé dans notre modèle corrèle également avec une modification du réseau de cytokines caractérisé par une nette augmentation de la sécrétion de CCL5 et de CCL2. En conclusion, cette étude met en évidence le rôle de HIF-1α dans le contrôle de la croissance et le remodelage du paysage immunitaire du mélanome B16-F10. Elle indique la possibilité de combiner un inhibiteur de HIF-1α avec une immunothérapie basée sur le blocage des points de contrôle immunitaire pour étendre leur efficacité et leur bénéfice thérapeutiques à un plus grand nombre de patients cancéreux
Impact of Targeting the Binding Domain of HIF-1α to HIF-1β on the Immune Landscape of Melanoma.
No full textL’hypoxie est une caractéristique majeure des tumeurs solides et elle est capable d’induire un microenvironnement tumoral immunosuppressif. Nous avons étudié l’impact de l’inhibition du domaine de liaison de HIF-1α avec HIF-1β sur le paysage immunitaire du mélanome murin B16-F10. Le ciblage de ce domaine de liaison inhibe l’activité transcriptionnelle de HIF-1α dans les cellules B16-F10 in vitro. In vivo, l’inhibition de l’activité transcriptionnelle de HIF-1α dans le mélanome B16-F10 montre une diminution significative de la croissance tumorale et une amélioration consistante de la survie des souris. La croissance tumorale est restaurée dans les souris immunodéficientes, soulignant l’importance du système immunitaire dans le contrôle de la croissance du mélanome. L’étude du phénotype des cellules immunitaires intra-tumorales révèle une augmentation de l’infiltration des cellules Natural Killer (NK), des lymphocytes T CD4+, des T régulateurs, des macrophages de type M1 et M2 et des cellules dendritiques lorsque l’activité transcriptionnelle de HIF-1α est inhibée. La déplétion de cellules NK dans notre modèle expérimental restaure la croissance tumorale, soulignant le rôle des NK dans la surveillance du mélanome B16-F10. Le changement du paysage immunitaire observé dans notre modèle corrèle également avec une modification du réseau de cytokines caractérisé par une nette augmentation de la sécrétion de CCL5 et de CCL2. En conclusion, cette étude met en évidence le rôle de HIF-1α dans le contrôle de la croissance et le remodelage du paysage immunitaire du mélanome B16-F10. Elle indique la possibilité de combiner un inhibiteur de HIF-1α avec une immunothérapie basée sur le blocage des points de contrôle immunitaire pour étendre leur efficacité et leur bénéfice thérapeutiques à un plus grand nombre de patients cancéreux.Hypoxia is a major feature of solid tumors and is able to induce a tumor immunosuppressive microenvironment. Here, we investigated the impact of inhibiting of the binding domain of HIF-1α to HIF-1β on the immune landscape of B16-F10 melanoma. Targeting this binding domain inhibits the transcriptional activity of HIF-1α in B16-F10 cells in vitro. In vivo, inhibiting the transcriptional activity of HIF-1α in B16-F10 melanoma shows a significant decrease in tumor growth and a consistent improvement in mice survival. Tumor growth is restored in immunodeficient mice, highlighting the critical role of the immune system in controlling melanoma growth. The phenotyping of intra-melanoma immune cells reveals an increase in Natural Killer (NK), CD4+ T cells, regulatory T cells, M1 and M2 macrophages and dendritic cells. NK depletion restores tumor growth in our experimental model, highlighting the role of NK cells in melanoma surveillance. The alteration of the immune landscape that we observed also correlates with a clear increase of secreted CCL5 and CCL2. In conclusion, this study highlights the role of HIF-1α in controlling the growth and the immune landscape of B16-F10 melanoma. It indicates the opportunity of combining HIF-1α inhibitors with immune checkpoint blockade to extend immune checkpoint blockade efficiency and therapeutic benefit to a larger number of cancer patients
Etude exploratoire du marché marocain des produits cosmétiques, techniques de soins et coaching bien-être
No full textReminiscences of a radio astronomer
No full textInternational audienceThe author belongs to the second generation of radio astronomers. He started observing in 1954 with a German Riese-Würzburg radar transformed into a radio telescope, then in 1959-1963 with a two- Würzburg variable-spacing interferometer. He participated in the construction of the Nançay Large Radio Telescope, and used the Owens Valley Observatory interferometer during a stay in Caltech (1968-1969). He was deeply involved in the genesis of the French-German-Spanish Institute of Radio Astronomy at Millimeter waves (IRAM). His contacts with radio astronomers worldwide are described. In recent years, he participated in a series of seven papers devoted to the history of radio astronomy in France, published in this journal
Birth, evolution and death of stars
No full textIt has been known for a long time that stars are similar to our Sun. But it was only in 1810 that they were shown to be made of an incandescent gas. The chemical composition of this gas began to be determined in 1860. In 1940, it was demonstrated that the energy radiated by the stars is of thermonuclear origin. How stars form from interstellar matter and how they evolve and die was understood only recently, with our knowledge still incomplete. It was also realized recently that close double stars present a wide variety of extraordinary phenomena, which are far from being completely explored. This book explains all these aspects, and also discusses how the evolution of stars determine that of galaxies. The most interesting observations are illustrated by spectacular images, while the theory is explained as simply as possible, without however avoiding some mathematical or physical developments when they are necessary for a good understanding of what happens in stars. Without being a textbook for specialists, this book can be profitably read by students or amateurs possessing some basic scientific knowledge, who would like to be initiated in-depth to the fascinating world of stars. The author, an emeritus astronomer of the Paris Observatory, worked in various domains of astronomy connected with the subject of this book: interstellar matter and evolution of stars and galaxies. He directed the Marseilles observatory from 1983 to 1988 and served for fifteen years as Chief Editor of the professional European journal Astronomy & Astrophysics. He has written many articles and books about physics and astronomy at different levels
Atypical chemokine receptor 2 expression is directly regulated by hypoxia inducible factor-1 alpha in cancer cells under hypoxia
No full textAbstract Lack of significant and durable clinical benefit from anti-cancer immunotherapies is partly due to the failure of cytotoxic immune cells to infiltrate the tumor microenvironment. Immune infiltration is predominantly dependent on the chemokine network, which is regulated in part by chemokine and atypical chemokine receptors. We investigated the impact of hypoxia in the regulation of Atypical Chemokine Receptor 2 (ACKR2), which subsequently regulates major pro-inflammatory chemokines reported to drive cytotoxic immune cells into the tumor microenvironment. Our in silico analysis showed that both murine and human ACKR2 promoters contain hypoxia response element (HRE) motifs. Murine and human colorectal, melanoma, and breast cancer cells overexpressed ACKR2 under hypoxic conditions in a HIF-1α dependent manner; as such overexpression was abrogated in melanoma cells expressing non-functional deleted HIF-1α. We also showed that decreased expression of ACKR2 in HIF-1α-deleted cells under hypoxia was associated with increased CCL5 levels. Chromatin immunoprecipitation data confirmed that ACKR2 is directly regulated by HIF-1α at its promoter in B16-F10 melanoma cells. This study provides new key elements on how hypoxia can impair immune infiltration in the tumor microenvironment
The evolution of the mass-metallicity relation in SDSS galaxies uncovered by astropaleontology
No full textMarangoni destabilization of bidimensional-confined gas-liquid co-flowing streams in rectangular microfluidic channels
No full textInternational audienceIn microchannels, the stability of a fluid jet injected into another immiscible fluid strongly depends on its degree of geometric confinement. When the width of the jet, w, is larger than the channel height, H, the surface tension driven Rayleigh-Plateau instability is suppressed so that the 2D (bidimensional)-confined jet is absolutely stable and never collapses into bubbles (or drops) in contrast to what occurs when w ≤ H [Dollet et al., "Role of the channel geometry on the bubble pinch-off in flow-focusing,"Phys. Rev. Lett. 100(3), 034504 (2008); Guillot et al., "Stability of a jet in confined pressure-driven biphasic flows at low Reynolds number in various geometries,"Phys. Rev. E 78(1), 016307 (2008)]. We here demonstrate both experimentally and theoretically that this picture is, indeed, no longer valid when Marangoni effects are considered. We experimentally show that the addition of small length alcohol molecules into the liquid phase destabilizes a 2D-confined gas-water microfluidic stream (w > H), leading to the generation of steady non-linear waves and further to the production of bubbles. Using a simple hydrodynamic model, we show through a linear analysis that the destabilization of the gas stream may result from a Marangoni instability due to the fast adsorption of the alcohol molecules, which occurs on a timescale comparable to that of the microfluidic flow. © 2023 Author(s)
Coupled HgSe colloidal quantum wells through a tunable barrier: a strategy to uncouple optical and transport band gap
No full textInternational audienceAmong semiconductor nanocrystals (NCs), 2D nanoplatelets (NPLs) are a special class of nanomaterials with well controlled optical features. So far most of the efforts have been focused on wide band gap materials such as cadmium chalcogenide semiconductors. However, optical absorption can be pushed toward the Infra-Red (IR) range using narrow band gap materials such as mercury chalcogenides. Here we demonstrate the feasibility of a core/shell structure made of a CdSe core with two HgSe external wells. We demonstrate that the optical spectrum of the heterostructure is set by the HgSe wells and this, despite the quasi type II band alignment which makes the band edge energy independent of the inner core thickness. On the other hand, these core/shell NPLs behave, from a transport point of view, as a wide band gap material. We demonstrate that the introduction of a wide band gap CdSe core makes the material less conductive and with a larger photoresponse. Hence the heterostructure presents an effective electric band gap wider than the optical band gap. This strategy will be of utmost interest to design infrared effective colloidal materials for which the reduction of the carrier density and the associated dark current is a critical property
Evolução química e história de formação estelar no universo local
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas, Programa de Pós-Graduação em Física, Florianópolis, 2010Analisamos as galáxias do Sloan Digital Sky Survey com o nosso código de síntese espectral Starlight. O Starlight acha a combinação de populações estelares simples de diferentes idades e metalicidades que melhor modela o espectro de uma galáxia. Ele permite derivar vários parâmetros associados a uma galáxia, como a massa em estrelas, a história de formação estelar e a evolução química. A partir do espectro residual puramente nebular (subtraindo do espectro observado o modelado), medimos as linhas de emissão, das quais derivamos propriedades do gás dentro das galáxias. Estudamos a evolução das galáxias com formação estelar. Constatamos que as galáxias de maior massa formaram suas estrelas e seus metais mais rapidamente. A evolução da metalicidade das estrelas é estudada diretamente. Calibramos também a taxa de formação estelar atual medida pela síntese com a medida pela luminosidade de Halfa. Derivamos a relação massa estelar-metalicidade estelar (M*-Z*) em diferentes redshifts. Esta é a primeira vez que a relação M*-Z* é calculada para o mesmo conjunto de galáxias. Observamos que a metalicidade estelar observada tem uma evolução compatível com um modelo simples de evolução química de caixa fechada. Para as galáxias classificadas como LINERs, encontramos que a luminosidade observada em Halfa é compatível com o número de fótons ionizantes emitidos pelas populações estelares velhas dessas galáxias. Este resultado implica em uma profunda revisão da taxa de atividade nuclear nas galáxias do Universo local
